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目的:探讨食管癌及其癌前病变Barrett食管组织中抑癌基因SLC5A8甲基化状态及表达情况。方法:分别采用甲基化特异性PCR法(MSP)及RT-PCR法检测45例食管癌、癌旁及切缘组织SLC5A8甲基化及基因表达情况;采用MSP法检测42例Barrett食管及其正常食管黏膜中SLC5A8甲基化情况。结果:45例食管癌组织的甲基化阳性率显著高于癌旁及切缘组织,χ2=31.3,P<0.01。42例Barrett食管甲基化阳性率显著高于其正常食管黏膜,χ2=8.23,P<0.01。食管癌的甲基化阳性率与Barrett食管的甲基化阳性率之间差异有统计学意义,χ2=9.59,P<0.01。31例SLC5A8甲基化阳性的食管癌组织中仅有2例检测到SLC5A8表达;而14例阴性标本中有10例检测到SLC5A8表达,甲基化与SLC5A8表达呈负相关,r=-0.572。SLC5A8甲基化阳性的食管癌组织中SLC5A8基因表达率显著低于甲基化阴性的食管癌组织,χ2=21.17,P<0.001。结论:抑癌基因SLC5A8的甲基化率在食管正常黏膜、Barrett食管、食管癌的不同病理进展阶段呈现升高趋势,而SLC5A8表达则呈下降趋势。甲基化是使其失活而抑制SLC5A8表达的重要因素,并且可能是食管癌发生及Barrett食管演变为食管癌的一个早期分子事件。
Objective: To investigate the methylation status and expression of tumor suppressor gene SLC5A8 in esophageal and precancerous lesions of Barrett’s esophagus. Methods: Methylation-specific PCR (MSP) and RT-PCR were used to detect the methylation and gene expression of SLC5A8 in 45 cases of esophageal cancer, paracancer and marginal tissue. 42 cases of Barrett’s esophagus and its normal SLC5A8 methylation in esophageal mucosa. Results: The positive rate of methylation in 45 cases of esophageal cancer tissues was significantly higher than that in adjacent tissues and marginal tissues (χ2 = 31.3, P <0.01). The positive rate of Barrett ’s esophagus was significantly higher than that of normal esophageal mucosa (χ2 = 8.23) , P <0.01. The methylation positive rate of esophageal cancer and Barrett’s esophagus methylation positive rate between the difference was statistically significant, χ2 = 9.59, P <0.01.31 SLC5A8 methylation-positive esophageal cancer tissue only 2 cases To SLC5A8, while SLC5A8 was detected in 10 out of 14 negative samples. Methylation was negatively correlated with SLC5A8 expression (r = -0.572). SLC5A8 methylation-positive esophageal cancer SLC5A8 gene expression was significantly lower methylation-negative esophageal cancer tissue, χ2 = 21.17, P <0.001. Conclusion: The methylation rate of tumor suppressor gene SLC5A8 shows an increasing trend in different pathological stages of esophageal normal mucosa, Barrett ’s esophagus and esophageal cancer, while SLC5A8 expression shows a decreasing trend. Methylation is an important factor that inactivates SLC5A8 expression and inhibits the expression of SLC5A8, and may be an early molecular event of esophageal carcinogenesis and evolution of Barrett’s esophagus into esophageal cancer.